Recent studies suggest that the naturally occurring melanotropins and antimelanotropins of the CNS, operating through cAMP and cGMP, participate in the regulation of brain metabolism. The proposed investigation will answer these questions: What are the structures of each extrahypophyseal melanotropin and antimelanotropin? Where are they located in the brain, where do they enter and leave the CSF, in what brain regions, cells and organelles do they localize, by what mechanisms do they then influence concentrations of cAMP and CGMP? How are these relationships disturbed in hydrocephalus, diffuse brain disease with psychomotor retardation, and other neurologic diseases? Previous work on behavioral effects of melanotropic peptides, on endocrine and behavioral effects of melatonin, and on CSF in patients with neurologic disease, indicate that the data forthcoming from the proposed experiments will provide new information about the molecular mechanisms of normal learning and memory, and about the pathologic conditions of delayed puberty, hydrocephalus, and psychomotor retardations.